2.6 Malignant bone tumours

Primary malignant bone tumours account for 1% of cancer deaths. The incidence for the three most common excluding myeloma is only nine per million of population per year. As a result all primary malignant bone tumours are best managed at one of the five centres directly funded by The National Commissioning Group.

All such patients are managed by a multidisciplinary team and, where appropriate, entered into national and international trials aimed at improving survivorship and achieving maximum function.

Patients present with a variety of symptoms including pain, swelling, and loss of function. In children and adolescents, making a diagnosis of ‘growing pains’ must be a diagnosis of exclusion, and all clinicians should investigate thoroughly patients that complain of ‘night pain’.

Patients presenting with malignant bone tumours usually have a mass which increases in size. This may happen slowly over a period of years or months or more quickly in a matter of weeks. These tumours are usually painless until the late stages. Any mass greater than 5cm in size that lies deep to the fascia and is increasing in size, should be investigated as a potential malignant tumour until proved otherwise. Again the management should involve a multidisciplinary team compromising the surgeon, and a radiologist, pathologist, oncologist, and radiotherapist. Again, for the best outcomes bone and soft tissue tumours are best managed in specialist centres.

Chondrosarcoma is a malignant tumour of cartilaginous origin, in which the tumour matrix formation is chondroid in nature.

Lesions are designated as primary when they arise de novo or as secondary when they occur within a pre-existing lesion such as an enchondroma or osteochondroma. The vast majority (greater than 85%) are primary central chondrosarcomas, designated as such based on their location centrally within the medullary cavity. A minority (up to 15%) of conventional chondrosarcomas develop from the surface of bone, most of them as a result of malignant transformation within the cartilage cap of a pre-existing osteochondroma. These are therefore called secondary peripheral chondrosarcomas. A minority (less than 1%) occur at the surface of bone, possibly of periosteal origin, and are designated periosteal chondrosarcoma. Their histology is similar to that of conventional chondrosarcoma.

Chondrosarcoma is the second most frequent primary malignant tumour of bone, representing approximately 25% of all primary osseous neoplasms.

The incidence rate of chondrosarcoma is dependent on patient age, peaking at eight cases per million of population in those aged 80–84 years. The incidence in children is low. Most tumours arise in patients older than 40 years. The exact cause of chondrosarcoma is not known. There may be a genetic or chromosomal component that predisposes certain individuals to this type of malignancy.

The following is a list of some benign conditions that may be present when chondrosarcoma occurs:

A slight male predilection exists, with a male to female ratio of 1.5–2:1.

Tumours are predominantly located in the pelvis, femur, humerus, ribs, scapula, sternum, or spine. In tubular bones, the metaphysis is the most common site of origin. The proximal metaphysis is more frequently involved than the distal end of the bone. Chondrosarcoma is rare in the hands and feet and if it occurs, does so as a complication of a multiple enchondromatosis syndrome.

The most common symptom at presentation is pain, which is often present for months and typically dull in character. It may be worse at night and classically described as being relieved by taking anti-inflammatories. Local swelling may be present, and when the tumour occurs close to a joint, effusion may be present, or movement may be restricted. The average duration of symptoms prior to presentation is 1–2 years. The tumour occasionally presents as a pathological fracture.

The distinction between benign and malignant cartilaginous lesions can be difficult. For the distinction between enchondroma and central grade I chondrosarcoma, conventional radiography is not reliable. Dynamic contrast-enhanced magnetic resonance imaging (MRI) shows greater sensitivity, although an absolute distinction between benign and malignant cannot be made on radiological grounds alone.

The locations and radiographic appearances of the different chondrosarcoma subtypes are often characteristic, with the mineralized chondroid matrix as a punctate or ring-and-arc pattern of calcifications that may coalesce to form a more radiopaque flocculent pattern of calcification and aggressive features of endosteal scalloping and soft tissue extension (Figure 2.6.1).

Computed tomography (CT) and MRI are indispensable adjunct tools for optimizing tumour characterization. Evidence of a large unmineralized soft tissue mass associated with a lesion with radiological features indicative of a chondrosarcoma should raise the level of suspicion for dedifferentiation.

Central and peripheral chondrosarcomas are histologically similar, and for both, three different grades are discerned (grade 1 represents the least aggressive in terms of histological features, and grade 3 represents the most aggressive) which is at present the best predictor of clinical behaviour. Recurrence of low-grade chondrosarcoma bears the risk for tumour progression toward a higher grade or even dedifferentiation, with a severe adverse prognosis.

Central and peripheral chondrosarcomas differ at the molecular genetic level. The exostosin (EXT) genes, causing multiple osteochondromas, are involved in the origin of osteochondroma and peripheral chondrosarcoma. In contrast, in the far more common central chondrosarcoma, EXT is not involved, and the initiating event is still unknown.

In addition to conventional chondrosarcoma, several rare subtypes of chondrosarcoma are discerned, together constituting 10–15% of all chondrosarcomas. These include:

For all grades and subtypes of non-metastatic chondrosarcoma, complete surgical treatment offers the only chance for cure. Wide, en bloc excision is the preferred surgical treatment of intermediate- and high-grade chondrosarcoma cases. However, wide excision can lead to considerable morbidity and a demanding reconstruction, depending on the location. On the other hand, in low-grade chondrosarcoma, extensive intralesional curettage followed by local adjuvant treatment, for example, phenolization or cryosurgery (liquid nitrogen), and filling the cavity with bone graft or PMMA (polymethylmethacrylate) cement has promising long-term clinical results and satisfactory local control. In some cases of low-grade chondrosarcoma, intralesional excision may not be adequate, for example, because of large size or an intra-articular or pelvic localization. In these cases, wide resection remains the preferable choice for local therapy. Metastases are rare in low-grade chondrosarcoma of the long bones. In the case of soft tissue involvement in chondrosarcoma grade I, wide en bloc resection is recommended.

In patients with multiple exostoses the development of secondary peripheral chondrosarcoma is rare (assumed in the literature to be less than 2%) and usually presents after skeletal maturity. Complete surgical removal of the cartilage cap with the pseudocapsule has excellent long-term clinical and local results.

The prognosis for patients with dedifferentiated chondrosarcoma is still poor, despite adequate wide surgical resection and adjuvant systemic therapy.

Chondrogenic tumours are considered relatively radiotherapy (RT) resistant. RT can be considered in two situations: after incomplete resection, aiming at maximal local control (curative), and in situations where resection is not feasible or would cause unacceptable morbidity (palliative).

Chemotherapy is generally not effective in chondrosarcoma, especially in the most frequently observed conventional type and the rare (low-grade) clear cell variant. Chemotherapy is only possibly effective in mesenchymal chondrosarcoma, and is of uncertain value in dedifferentiated chondrosarcoma; both subtypes are rare and bear a poor prognosis.

The prognosis for chondrosarcoma depends on the grade of the lesion and the attainment of complete excision of the tumour. For lower-grade chondrosarcomas, prognosis is very good (90% 5-year survival) after adequate local control. There is a low incidence of pulmonary metastasis if the primary lesion is widely resected. Metastasis to other bones can occur, but is much less common. Dedifferentiated chondrosarcoma has a uniformly poor prognosis (less than 10% 1-year survival).

Osteosarcomas can be subdivided into intramedullary, cortical (either on or in), or arising in pre-existing pathology. Intramedullary osteosarcomas include high- and low-grade osteosarcoma as well as telangiectatic osteosarcoma. Cortical lesions are subdivided into surface lesions, such as the parosteal and variable grade periosteal osteosarcomas or the rare intracortical osteosarcoma. Secondary osteosarcomas occur in pre-existing irradiated tissue beds, infection, infarction, Paget’s, fibrous dysplasia, or other bony lesions. Less common lesions include multifocal osteosarcoma as well as soft tissue osteosarcoma.

Incidence is approximately five per million population, and three per million in those less than 20 years. Although described as bimodal, the majority of cases occur in the rapidly growing bones of children and young adults. Common sites for osteosarcoma are the metaphyses of the distal femur, proximal tibia, proximal humerus, proximal femur as well as the mandible. Despite micro-metastases, which are common, patients tend not to be systemically unwell. Mass and pain are the most common presenting features.

Plain film evaluation confirms the extent of mineralized bone destruction, the osteolytic and blastic nature of the lesion, periosteal elevation, secondary ossification and soft tissue extension. Bone destruction is more extensive than films portray but the diagnostic sensitivity, cost, and widespread availability of radiographic plain film evaluation makes it a mandatory initial imaging modality (Figures 2.6.2 and 2.6.3).

MR evaluation is of major benefit to assess the extent of intra- and extraosseous tumour infiltration. It also enables tumour relationship to neurovascular structures to be determined, which affects limb-salvage decision-making during preoperative planning. Tumour can be separate from, in contact with, displacing, effacing partially or completely encasing the neurovascular bundle. If vasculature integrity needs further description appropriate angiography is requested.

A bone scan and CT chest are used to detect multifocal sites and chest metastases respectively.

Conventionally osteosarcomas are mineralized centrally with more immature bone at the periphery. The heterogeneous behaviour of conventional osteosarcoma is represented in the cellular population. Most commonly mixed, cell type can also be predominantly osteo-, chondro-, or fibroblastic, affecting necrosis rates following chemotherapy. The presence of osteoid and malignant stromal cells is needed to diagnose osteosarcoma. Cells may have a lace, trabecular, or sheet-like pattern

These constitute 80% of all osteosarcomas leading to the descriptive use of ‘conventional’ or ‘classic’. They are the subtype upon which the majority of survivorship analyses are made. Most have penetrated the cortex and have an associated soft tissue mass, making this a stage IIB lesion. This more common subtype presents with CT detectable pulmonary metastases in 20% of patients.

An aggressive, osteolytic, expansile lesion that can radiologically appear identical to an aneurysmal bone cyst. They contain fewer, but highly malignant cellular elements and account for 3.5–11% of osteosarcamatous cases.

Affecting multiple bones significantly worsens the prognosis. It is rare, and detectable with whole-body bone scan or perhaps in the future, whole-body MRI. Metachronous lesions occur years after the primary lesion and are differentiated from recurrence by occurring at a different site. Multifocal lesions are in different bones. It is not yet discernable whether multicentric osteosarcoma represents multiple de novo tumours or multiple bone metastases within a narrow time window from a solitary bone primary site.

Skip metastases which are seen in 10% of lesions, are detectable in the same bone at the same time, but can be at differing stages of local bony destruction.

Low-grade lesion classically over the posterior aspect of the distal femur or the proximal humerus. Differentiated from a sessile osteochondroma in that the osteosarcoma is on the bone surface and not in uniform continuity with the cancellous bone of the metaphysis. Seen more commonly in the third or fourth decade and slightly more so in females, with radiographic features of ossification and lobulation. Can be confused with synovial osteochondromatosis or myositis ossificans. Depending on the extent of bone involvement treatment is either by shark-bite resection or wide excision. Chemotherapy is only instituted if high-grade or de-differentiated areas are found on histological analysis.

Unlike the other groups this tends to occur in the diaphysis of the long bones and consists mainly of chondroblastic cells. Ninety-five per cent involve the distal femur or proximal tibial meta-diaphysis. It is usually of intermediate grade, and typically arises from the anteromedial bone portion.

Classically arises in 1% of patients with Paget’s disease. Its diagnosis can be expedited by appreciating that soft tissue extension, detectable on MRI, is the hallmark of malignant transformation. The advanced age of pagetoid patients makes chemotherapy less tolerable, significantly worsening the prognosis for these patients. Less than 5% of secondary osteosarcomas occur in irradiated bone.

Chemotherapy and surgery form the mainstay of treatment. Limb salvage is usually possible in up to 80% of patients. Prior to the introduction of chemotherapy mortality from osteosarcoma was approximately 85%, even with radical resection or amputation. This is a representation of its propensity to micro metastasize early in its natural history. Chemotherapy kills the malignant cells and aims to improve patient survivorship and ultimately cure. Surgery compliments this by obtaining a margin negative resection, followed by bony and soft tissue reconstruction.

New chemotherapy protocols, with appropriate surgery, have produced an approximate 75% survival at 5 years. There is no difference in survival if chemotherapy is administered prior or post surgery. This is in accordance with the presence of non-detectable lung micro-metastases and the tumour cell’s response to chemotherapy being ultimately responsible for the patient prognosis. Common chemotherapeutic agents include cisplatin, doxorubicin, ifosfamide, and methotrexate. Immunostimulants, immunotherapy, cytotoxic T-cells, and monoclonal antibody therapy treatments are ongoing but have yet to yield a reproducible and consistent survival improvement.

Surgical resection aims to achieve a complete tumour resection with an appropriate margin, without tumour spillage or neurovascular damage that may render a salvaged limb functionless. If this is not possible, amputation is considered. It is not a ‘failure’ to amputate and just as much careful preoperative planning, operative attention to detail, and postoperative care is warranted as any limb salvage operation.

The major factors associated with a bad prognosis in osteosarcoma are a poor response to chemotherapy (less than 90% necrosis), skip or pulmonary metastases (stage), and the tumour grade. Other poor outcomes are associated with large tumours, axial/pelvic and central tumours, older patients, and tumours in pre-existing pathological tissues. Patient survivorship for conventional osteosarcoma remains at 75% at 5 years. Of the total number of recurrences, approximately 5% occur after 5 years. Follow-up protocols vary but most patients need to be reviewed every 3 months for the first 2 years, 6-monthly up to 5 years, and then yearly reviews can continue.

Ewing’s sarcoma is a cluster of tumours consisting of intra- and extraosseous Ewing’s sarcoma, primitive neuroectodermal tumour (PNET), Askin’s tumour (PNET of chest wall), periosteal Ewing’s, and neuroepithelioma. Cell origin is primarily neural. The tumour is often aggressive but is usually chemo- and radiosensitive.

The incidence is approximately two per million, affects 5–20-year-olds and has an increased prevalence in Caucasians.

Ewing’s sarcoma can present with localized features of pain, mass, and pathological fracture, as well as systemic constitutional symptoms of fever, weight loss, or malaise. The long bones, pelvis, vertebrae, ribs, or clavicle are most commonly affected, with the femur, tibia, humerus, and fibula involved in decreasing frequency. Like osteosarcoma, approximately 20% of patients present with metastatic disease.

Classically there is laminated periosteal ‘onion-skinning’ in the diaphysis of a long bone in association with a permeative moth-eaten bony radiolucent lesion (Figure 2.6.4). These appearances are also very similar to infection and with the raised inflammatory markers, can cause a delay in reaching the correct diagnosis.

MR describes extent of marrow infiltration, soft tissue extension, solid and necrotic tumour elements, cortical thickening, and periosteal reaction.

The absence of osteoid formation can produce liquid pus-like material on biopsy of the soft tissue component. Sheets of small, undifferentiated, round cells with prominent nuclei and poorly visualized cytoplasm make other lesions such as lymphoma, myeloma, histiocytosis, rhabmyosarcoma, metastatic neuroblastoma, small-cell osteogenic sarcoma, and mesenchymal chondrosarcoma all possible diagnoses. The Ewing’s groups of tumours have a 95% sensitivity of surface expression of p30/32 MIC2 antigen and CD99. The t(11:22) translocation is found is 90% of patients. PNET is differentiated from Ewing’s both histologically by Homer Wright rosettes as well as positive staining of the neural S100 marker with PNET lesions.

Local, multicentric, and metastatic Ewing’s sarcoma is treated with a combination of systemic (chemotherapy) and local (surgery with or without radiotherapy) therapies. Chemotherapeutic regimens include the use of actinomycin, cyclophosphamide, doxorubicin, etoposide, and ifosfamide. These have improved survivorship and have necessitated local control measures in the last 30 years. The treatment modality depends on the patient medical status, tumour location, and extent of spread.

Long bone lesions that can be resected safely are amenable to joint reconstruction. Pelvic lesions can present particular challenges, especially in the paediatric population. Open growth plates mean that resection with or without joint reconstruction can leave children with considerable pelvic girdle and lower limb deficits. Resection (or indeed complete hemipelvic disarticulation), extracorporeal radiotherapy, and re-implantation is possible given the radiosensitive nature of Ewing’s sarcoma. Re-implantation techniques are similar to allograft implantation. Viable tumour cells are ablated using radiotherapy leaving the remaining scaffold available for host bone recolonization.

The presence of disseminated disease remains the most important factor in predicting survival. Approximate 3-year survival rates in patients with lung metastases on presentation are 40%, 70% in isolated disease, and 30% with disseminated disease. Any survivorship figures need to be interpreted with caution. Clearly small appendicular tumours have a completely different prognosis to large axial tumours or those located within the pelvis. Follow-up between both oncologist and orthopaedic surgeon follows the same regimen as for osteosarcoma.

Myeloma of bone is of haematological origin and is managed primarily by haematological oncologists. Causes have been attributed to radiation exposure and a genetic predisposition. If isolated it is termed plasmacytoma or multiple myeloma if disseminated.

Lesions produce a neoplastic single clone proliferation of plasma cells that produce a monoclonal immunoglobulin. The orthopaedic team is involved in managing the plasma cell-induced osteolytic skeletal destruction and secondary bony structural failure. Other medical ramifications include hypercalcaemia, anaemia, renal failure, hyperviscosity syndrome, or recurrent bacterial infections.

With an incidence of four per 100 000 per year, multiple myeloma is the most common primary bone tumour in adults. It is primarily a disease of patients after their fourth decade, with the median incidence at age 65. It is more common in black patients presenting with fever, pain, or weakness. It can be asymptomatic. Additional orthopaedic presenting complaints include axial, thoracic, or appendicular limb pain as well as secondary effects such as spinal cord compression or pathological fracture.

Extramedullary plasmacytoma presents as a soft tissue mass.

Normocytic, normochromic anaemia is found at diagnosis in approximately 70% of patients. Leucopenia and thrombocytopenia are less common. Erythrocyte sedimentation rate is often raised. Urinary Bence Jones protein and an aberrant serum paraprotein (or M-protein) is found in 90% of patients at presentation. Plasma electrophoresis enables quantitative measurement to secure a diagnosis and disease monitoring.

Differential diagnoses include metastatic carcinoma, lymphoma, monoclonal gammopathy of unknown significance (MGUS), smouldering multiple myeloma (SMM), acute leukaemia, or POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin anomalies) syndrome.

Minimal diagnostic criteria consist of more than 10% plasma cells in bone or a plasmacytoma plus one of serum or urine paraprotein or lytic bone lesions. The International Myeloma Working Group has staged the disease using B₂ microglobulin (MHC class I) levels as it is an overall marker for body tumour burden. Stage I is classified as a level less than 3.5mg/L, II lies between 3.5–5.5mg/L, and stage III more than 5.5mg/L.

Plain film evaluation demonstrates punched-out lytic lesions or fractures in 75% of patients at diagnosis (Figure 2.6.5). Technetium-99m-labelled bone scans are usually cold hence conventional radiographs are used for the detection of lytic lesions with no surrounding sclerosis. The lateral skull is classic for the ‘pepper-pot’ appearance. CT and MRI are more sensitive and may be useful when skeletal pain is atypical and radiographs show no abnormalities.

Histological analysis reveals large basophilic cytoplasmic plasma cells containing rounded or oval eccentric nuclei with clumped chromatin and a perinuclear halo.

Most patients with focal plasmacytoma undergo surgery if feasible, radiation, and subsequent observation. Multiple myeloma presents challenges at multiple levels and care is targeted on disease control and suppression, the extent of which depends on the disease progression and patient status. The anaemia is managed with erythropoietin and bony destruction slowed by bisphosphonates.

Asymptomatic patients with low B₂ microglobulin levels are observed. Symptomatic patients receive chemotherapy and haematopoietic stem-cell transplantation.

Orthopaedic input is usually at the pre-, impending, or postfracture stage. Fracture union in the presence of pathological bone proceeds at varying rates in comparison to normal bone. Long, locked intramedullary nails form the mainstay of operative treatment.

Depending on the stage, median survival is 62 months for stage 1, 45 months for stage 2, and 29 months for stage 3 disease. Follow-up is with haematologists with a low threshold for orthopaedic consultation.

Fibrosarcoma is a tumour of mesenchymal cell origin that is composed of malignant fibroblasts in a collagen background. It can occur as a soft tissue mass or as a primary or secondary bone tumour. Fibrosarcoma was diagnosed much more frequently in the past; it is now more reliably distinguished histologically from similar lesions, such as desmoid tumours, malignant fibrous histiocytoma, malignant schwannoma, and high-grade osteosarcoma.

The two main types of fibrosarcoma of bone are primary and secondary. Primary fibrosarcoma is a fibroblastic malignancy that produces variable amounts of collagen. It is either central (arising within the medullary canal) or peripheral (arising from the periosteum). Secondary fibrosarcoma of bone arises from a pre-existing lesion or after radiotherapy to an area of bone or soft tissue. This is a more aggressive tumour and has a poorer prognosis.

Fibrosarcoma represents 10% of musculoskeletal sarcomas and less than 5% of all primary bone sarcomas.

Fibrosarcoma of bone usually affects the metaphysis of long bones in patients over 50 years of age. Presenting features include pain, mass effect, decreased range of movement, and fracture. Pre-existing pathological lesions or irradiated tissue needs to be considered with increased suspicion.

Fibrosarcoma of the soft tissues usually affects a wider age spectrum of patients than fibrosarcoma of the bone does, with an age range of 35–55 years. It often arises in the soft tissues of the thigh and the posterior knee. It is generally a large, painless mass deep to fascia and has an ill-defined margin.

Typically, an osteolytic, metaphyseal, eccentrically placed lesion associated with cortical destruction and soft tissue extension, with a marked absence of ossification or mineralization. MRI is the best modality for examining soft tissue masses and providing information about the local extent, lesion size, and involvement of the neurovascular structures. Fibrosarcoma of bone typically has extraosseous extension (Figure 2.6.6).

Well-differentiated forms have multiple plump fibroblasts with deeply staining nuclei in a rich collagen background. Intermediate-grade tumours have the typical herringbone pattern, showing the diagnostic parallel sheets of cells arranged in intertwining whorls. A slight degree of cellular pleomorphism exists.

High-grade lesions are very cellular, with marked cellular atypia and mitotic activity. The degree of cellularity, nuclear atypia, and pleomorphism are used to classify fibrosarcoma into grades 1–3. The higher grade 3 lesions are deemed to be malignant fibrous histiocytomas. In fact, some pathologists believe that the division between malignant fibrous histiocytoma, high-grade osteosarcoma, and fibrosarcoma may be artificial.

Grade 1 lesions are managed operatively without chemotherapy. Grade 2 lesions involve chemotherapy and resection. Grade 3 lesions follow malignant fibrous histiocytoma/osteosarcoma regimens. Radiation is administered in palliative cases and incomplete resections.

If all grades are included, primary fibrosarcoma of the bone has a worse prognosis than osteosarcoma, with a 5-year survival rate of 65%. In high-grade primary fibrosarcoma, the 10-year survival rate is less than 30%. Secondary fibrosarcoma is associated with a very poor outcome, the survival rate at 10 years being less than 10%.

For congenital fibrosarcoma of bone in children, the prognosis (which is related to age and to time to diagnosis) is much better, with the disease having long-term survival rates of grater than 50%.

Soft tissue fibrosarcoma is associated with a 40–60% survival rate at 5 years. The infantile form has an even better 5-year survival rate, in excess of 80%.

Primary lymphoma of bone (PLB) is a rare, malignant, neoplastic disorder of the skeleton. The vast majority of them are non-Hodgkin lymphoma (NHL), whereas primary Hodgkin lymphoma (HL) of bone is extremely rare.

Primary lymphomas of bone are uncommon malignancies (approximately 5% of primary malignant bone tumours and 5% of all cases of extra-nodal NHL). Comprehensive immunohistochemical studies are required to establish an accurate histological diagnosis of primary NHL of bone. Most cases of primary NHL of bone are classified as diffuse large B-cell lymphomas (DLBCL) in the World Health Organization (WHO) classification of haematological malignancies.

There is a marginal male preponderance. The incidence of disease is distributed fairly evenly in the second through to the eighth decades. Primary NHL of bone can arise in any part of the skeleton, but long bones (femurs, tibia) are the most common sites to be affected.

Patients with primary NHL of bone commonly present with local bone pain, soft tissue swelling, a mass, or a pathological fracture. Prolonged pain is the usual clinical symptom.

The WHO recognizes the following four groups of lymphoma involving bone:

Groups 3 and 4 would most likely represent metastatic involvement of bone.

PLB tumours produce osteoclast-stimulating factors that cause lytic bone destruction (Figure 2.6.7). The most common radiographic features include:

Sequestrum formation is a feature of PLB that can help to differentiate it from most other diagnostic possibilities. Sequestra have been reported in 11–16% of patients with PLB. Finally, involvement of adjacent bones is seen in 4% of cases.

After biopsy of the bone lesion confirms the diagnosis of lymphoma, CT scanning of the chest, abdomen, and pelvis is needed to exclude distant spread. The CT scan may be combined with positron emission tomography (PET), which is emerging as a possible modality for initial staging and follow-up. Technetium-99m (^99mTc) bone scintigraphy also can be used to look for additional sites of involvement.

The clinical features and radiological findings of PLB are usually non-specific, with the diagnosis relying principally on tissue histology.

The Rappaport classification system (1956) was based on light microscopic appearance. The Ann Arbor staging system, developed initially for HL, has been widely applied to the NHLs. This staging system is based on anatomic location and does not involve histology. Due to the advances of immunohistochemical markers there are now a myriad of new classification systems.

Treatment for PLB often involves radiation therapy to control the tumour in the affected bone. In certain instances, surgical intervention for control of the primary bone lesion may be desirable or necessary. Several studies indicate that patients with primary NHL of bone have a favourable outcome, especially when treated by combined modality therapy.

Combined modality therapy includes a method of local control, usually radiation therapy, and a systemic treatment, usually combination chemotherapy. Recurrence at the initial primary site is uncommon. Late, distant soft tissue metastases to lung, liver, and brain account for most of the mortality and much of the morbidity.

Average survival is 19–27 months for low-grade lymphoma and less than 11 months for high-grade tumours.

Malignant vasoformative tumours are rare. Three variants of malignant vascular tumours of bone are commonly described: haemangioendothelioma (angiosarcoma), haemangiopericytoma, and epitheloid haemangioendothelioma.

An uncommon malignant neoplasm characterized by rapidly proliferating, extensively infiltrating anaplastic cells derived from blood vessels and lining irregular blood-filled spaces. The term angiosarcoma may be applied to a wide range of malignant endothelial vascular neoplasms affecting a variety of sites. Angiosarcomas are aggressive and tend to recur locally, spread widely, and have a high rate of lymph node and systemic metastases. The rate of tumour-related death is high.

Bone angiosarcomas appear most often in adults (second to seventh decades of life). Bone and soft tissue angiosarcoma are also reported to be more frequent in males. Thirty-three per cent affect the axial skeleton, 33% in long bones, and the rest in the small bones of the hands and feet.

These tumours can be multifocal, or multicentric, involving multiple bones of the same extremity. Pain is commonplace. Presentation features include:

A solitary lesion (60% of cases) presents as a destructive lytic mass with irregular borders or a mixed lytic–sclerotic pattern and occasional bony expansion. It has a distinctive pattern of soap-bubble lesions because it frequently extends up and down the bone. CT scan is helpful in illustrating the permeative, invasive character of the radiographic lesions and shows their multiplicity.

The main problem in the diagnosis of angiosarcoma is histopath ological recognition. Microscopic findings include the presence of vascular spaces which are lined by atypical endothelial cells, with significantly increased numbers. Higher-grade lesions are more cellular and abnormal mitoses.

Surgical resection and radiation therapy are the standard treatment for localized disease. Treat high-grade lesions as malignant bone neoplasms, with a combination of radical en bloc excision followed by radiotherapy and/or chemotherapy.

All angiosarcomas tend to be clinically aggressive, difficult to treat, and are often multicentric. They have a high local recurrence rate and metastatic potential. They are often misdiagnosed, leading to a poor prognosis and a high mortality rate. The reported 5-year survival rate is around 20%.

Haemangiopericytomas are rare, typically low-grade sarcomas.

As with angiosarcomas the aetiology of haemangiopericytomas is largely unknown; they have been reported secondary to radiation, chemical exposure, and, rarely, burns or scars.

Haemangiopericytoma is a malignant tumour of mesenchymal origin that occurs in the extremities. Tumour typically spreads via haematogenous dissemination, primarily to the lungs. Metastatic disease is usually the cause of death.

Haemangiopericytomas primarily manifest as slow-growing, painless masses in the extremities, commonly the femur and proximal tibia. They can also occur in the pelvic fossa and the retroperitoneum.

Most documented cases occur within the third to fifth decades. They have been documented in children.

Additionally, 35% of skeletal tumours with oncogenic osteomalacia have been reported to be haemangiopericytomas. Oncogenic osteomalacia occurs with bone or soft tissue tumours and refers to the musculoskeletal symptoms of cramping and diffuse bone and muscle pain associated with electrolyte abnormalities, most notably hypophosphataemia.

With plain radiography, bony lesions predominantly present as intramedullary lytic masses. They may be well circumscribed, with a periosteal reaction or sclerotic border. They also may display cortical destruction, producing indeterminate borders with a honeycomb appearance. Findings of soft tissue haemangiopericytomas on plain films are usually non-specific. Bone scanning is indicated to exclude other sites of disease in patients who present with a bony haemangiopericytoma. MRI ± angiography should be used to distinguish between vascular malformations and tumours.

Haemangiopericytomas are neoplasms of pericytes that form solid sheets and nests around irregularly formed vascular channels. The vascular lining is normal and is composed of a single layer of non-malignant endothelial cells. Pericytes are of mesenchymal derivation and partially surround the endothelial cells of capillaries and small venules to assist blood flow regulation. These cells are located outside the connective-tissue compartment and are surrounded by their own basal lamina.

A diagnosis of haemangiopericytoma is made solely on the basis of architectural patterns exhibited histologically. Thus this type of tumour cannot be accurately distinguished from other neoplasms that have vascular characteristics, without such detailed histological information. The diagnosis of this tumour and evaluation of its clinical course remain complex challenges for tumour surgeons and histopathologists.

Treatment of haemangiopericytomas is based on the grade of the sarcoma.

Low-grade bone tumours require surgical resection and are not usually treated with chemotherapy. High-grade bone tumours may be treated with chemotherapy, but because of the rarity of these tumours, the direct benefit of treatment is unknown.

Soft tissue haemangiopericytomas are treated with surgical resection and radiation therapy to decrease local recurrence.

A low- to intermediate-grade vascular tumour composed of epithelioid endothelial cells. Epithelioid haemangioendothelioma is an extremely rare vascular bone tumour with a slow growth and poor prognosis. It represents 1% of all vascular neoplasms and is locally aggressive. Other proposed terms have included ‘sclerosing angiogenic tumour’.